Reply:
Authors: Winnie Yeo, Frankie K. F. Mo
Journal: Hepatology (2007)

We agree that a high hepatitis B virus (HBV) load prior to treatment is not the only but one of the significant adverse prognosticators for survival in patients with hepatocellular carcinoma (HCC) with chronic HBV infection undergoing chemotherapy.1 In response to the comment by Huo et al., analysis was conducted with incorporation of Cancer of the Liver Italian Program (CLIP) scores2 in our studied patient population. Upon univariate analysis, CLIP was found to be another prognosticator for survival in addition to the already reported pretreatment factors. Upon multivariate analysis, the factors significantly affecting survival were, again: total bilirubin (P = 0.0020; HR [hazard ratio] = 1.040 for every 1 μmol/L rise in level, 95% confidence interval [CI], 1.014-1.066), hepatitis C virus (HCV) infection (P = 0.0040; HR = 8.794, 95% CI, 2.003-38.616), high HBV DNA level (P = 0.0319; HR = 1.596, 95% CI, 1.041-2.447), and CLIP was also found to affect survival (P = 0.0030, HR = 1.314, 95% CI, 1.097-1.574). In the coexistence of HCC-related and HBV-related chronic liver disease, it is acknowledged that the cause of death for HCC patients cannot be completely attributable to the malignancy per se. Similarly, morbidities during and after chemotherapy in HCC patients cannot solely be attributable to treatment-related complications. As such, although the authors concluded that the causes of death were due to malignancy in 76% of the cases, and treatment-related complications in 6% of the cases, it would be highly unlikely that one could rule out HBV-associated chronic liver disease as an important contributing factor to the mortality and morbidity in our patient population. In the exploratory analysis, patients who developed severe hepatitis appeared to have the worst survival; this difference in clinical outcome was not found to be statistically significant and as discussed, this was presumably due to the relatively small number studied. However, the main objective of this part of the analysis remains hypothesis-generating, and a conclusive verdict could not be derived from analysis that remains exploratory. Interferon was included in PIAF chemotherapy (other agents included were cisplatin, doxorubicin and 5-fluorouracil) for its immunodulatory, antiproliferative and antiangiogenic effects.3 As discussed in our article, the dosage of interferon in the PIAF regimen was much lower than that used for the treatment of chronic HBV infection. Furthermore, conventional interferon had been shown to be less effective in Asian chronic HBV infection. Thus, it is unlikely to have a therapeutic effect on the chronic HBV infection in our HCC population, and is supported by the fact that rate of hepatitis was the same in both chemotherapy arms. The median baseline HBV DNA in PIAF-treated versus doxorubicin-treated patients were similar at 106.25 and 106.81 copies/mL, respectively; there was no difference in the rate of severe hepatitis between the 2 group of patients. In conclusion, the present study demonstrated that a high HBV load prior to treatment is one of the significant adverse prognosticators for survival in HCC patients with chronic HBV infection undergoing chemotherapy. It is our opinion that the data support the adoption of antiviral agents as part of the supportive therapy in an attempt to improve survival of these patients. Winnie Yeo*, Frankie K. F. Mo*, * Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.